Post on 26-Jan-2022
Advancing SDTM annotation through automation
Anja Kreis
Wolfgang Rohnert
Gerald Leahy
Nov 2020
Advancing SDTM annotation through automation | Nov 2020| | Company Confidential © 2020 AbbVie |
DISCLOSURE
2Advancing SDTM annotation through automation | Nov 2020| Company Confidential © 2020 AbbVie |
The support of this presentation was provided by AbbVie. AbbVie participated in the review and approval of the content.
Anja Kreis is an employee AbbVie and may own AbbVie stock.
Wolfgang Rohnert is an employee AbbVie and may own AbbVie stock.
Gerald Leahy works for AbbVie as a contractor and may own AbbVie stock.
Challenges and Business Impact
Manual vs automated process
aCRF creator – Overview
aCRF creator – Requirements and Guidelines
Challenges of manual process
Introduction aCRF
AGENDA
3Advancing SDTM annotation through automation | Nov 2020| Company Confidential © 2020 AbbVie |
Why not buy a commercial tool?
Annotated Case Report Forms (aCRF)
4Advancing SDTM annotation through automation | Nov 2020| Company Confidential © 2020 AbbVie |
Annotated Case Report Forms (aCRF) - Key CDISCsubmission deliverable.
Importance of the aCRF for regulatory agencies. Support FDA reviewer to find the origin of data variables.
Importance of the aCRF for study teamsØ SDTM annotation performed per study at
least two times:§ beginning of study for study team§ end of study for SDTM submission packageØ Use by Data Management/Data ScienceØ Use for creating ADaM datasets
Challenges of manual process
5Advancing SDTM annotation through automation | Nov 2020| Company Confidential © 2020 AbbVie |
Manual annotation takes a week or more per study.
Manual aCRFbookmark creation
usually takes several hours.
The work is done by highly qualified personal. Annotation is a complex
Process.
Knowledge needed in different tools. Each tool is
providing partial information which needs to be combined manually.
Validating annotations against submission
datasets are error prone activities.
Maintaining consistency across annotations
regarding size, color, font type.
Why not buy a commercial tool?
6Advancing SDTM annotation through automation | Nov 2020| Company Confidential © 2020 AbbVie |
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Tools on the market
• Use blank Case Report Form (CRF) document from Electronic Data Capture (EDC) system
• Often require pre-annotation ofthe form
• Cannot be linked to in-house systems
• Cannot handle complex pages• Entail updates of created
annotation
aCRF Creator
• Automated creation of SDTM annotated CRF
• CRF creation based on EDC system metadata instead of using blank CRF from EDC system
• Use of Metadata stored and maintained in Metadata Repository, no pre-annotation is needed
• Annotation based on study specific metadata from Clinical Data Repository (CDR)
• Complete annotation process is automated
Items not submitted shouldbe annotated with
text‚NOT SUBMITTED‘
aCRF creator – Regulatory Requirements
7Advancing SDTM annotation through automation | Nov 2020| Company Confidential © 2020 AbbVie |
Inlude treatmentassignment forms, when applicable
and map eachvariable on the CRF
to correspondingvariables in dataset
Include variable names and codingfor each CRF item
§ Regulatory Requirement documentsØ Technical Conformance Guide
Ø FDA‘s portable document PDF Specifications
aCRF creator – CDISC Guidelines
8Advancing SDTM annotation through automation | Nov 2020 | Company Confidential © 2020 AbbVie |
• Metadata Submission Guidelines v1.0 – CDISC SDS Metadata Team
aCRF should be bookmarked by form and by visit.
aCRF should not have databaseannotations on it.
aCRF must contain all final unique CRFpages/modules. It should not containblank pages.
Domain should have its annotation with2-letter domain code and domain name.
If more than one domain exists on a page, each domain , and all of its variables should be color-coded.
All text in the annotation that representvariable and domain names should becapitalized.
aCRF creator – Additional Guidelines
9Advancing SDTM annotation through automation | Nov 2020 | Company Confidential © 2020 AbbVie |
Domains [Domain Short Name] = [Domain Long Name]
Supplemental Qualifiers SUPPXX.QVALwhen QNAM = VARNAME
Appearance recommendations (font, color)
Test Codes e.g. VSORRES when VSTESTCD= “WEIGHT”, VSORRESU when VSTESTCD=“WEIGHT”
Additional Guidelines
aCRF Creator Overview – CRF creation
10Advancing SDTM annotation through automation | Nov 2020 | Company Confidential © 2020 AbbVie |
SAS webservice calls to receive study metadata from EDC System
Tool is a combination of shell scripts and SAS programs (SAS 9.4 on HP-UX)
New Strategy: map only needed elementsHTML tagging from EDC Tool had to be stripped out
SAS AUTOMAP attempted to generate XMLMAP -> too many unneeded elements were defined
Final conversion to PDF by PS2PDF
PDF format of each question label and response field based on length of annotation
aCRF Creator Overview – Access Metadata
11Advancing SDTM annotation through automation | Nov 2020 | Company Confidential © 2020 AbbVie |
Study specific metadata extracted to Clinical Data Repository (CDR)
Metadata (CDASH, SDTM, mappings, lookups) stored and maintained in MDR
FDF file containing annotations feeding from study specific metadata from Clinical Data Repository (CDR)
aCRF Creator Overview – Creation of Annotation
12Advancing SDTM annotation through automation | Nov 2020 | Company Confidential © 2020 AbbVie |
CRF label and response field coordinates based on annotation box width and height.Programming of annotation placement by trial and error until perfect coordinates found..
SAS used to generate all layers, the document layer produced by DATA _NULL_ in postscript format, so the bookmark layer (pdfmark) and annotation layer (FDF) can easily be appended. Script allows to automatically import FDF file to pdf File.
SAS macro reads through metadata received from EDC system and brings over all matching SDTM annotations from study specific metadata.
For annotation text field followinginformation needs to be
defined:• Box color, CRF page, Box
width and height • Annotation text font and
size, alignment, color
aCRF Creator - Bookmarking
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• Tool creates automated bookmarking of domains
Compiling SDTM domains within a
form, identifying the page, reversing the sort to present the bookmarks in the
desired order
Bookmark hierarchy is two tiered with
SDTM domain above form name, sorted by SDTM domain prefix
aCRF Creator – System Architecture Diagram
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Metadata Repository
Clinical Data Repository
Study Specific Metadata in Business Area (BA) Prod/QC
Study Metadata Global & StandardsLibrary Metadata
Source-to-Target Mappings & Rules
WebservicesEDC System Metadata as
XML file
EDC System
Pull Study Metadata & Create SAS Datasets
SourceSystem
Extract Study Metadata and create/load SAS datasets via XMLMAP Annotated
CRF
Target Study Metadata& Mappings
Metadata Load Utility
PL/SQL
MDR Integration Framework
aCRF Creator• eCRF PDF• FDF annotation File
eMail with Link to aCRF
Advancing SDTM annotation through automation | Nov 2020 | Company Confidential © 2020 AbbVie |
Global Lookup Table
aCRF Creator - UI overview
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• General overview of user interface
Advancing SDTM annotation through automation | Nov 2020 | Company Confidential © 2020 AbbVie |
Enter study or prefix of
study number
Select Study
Select CRF version
Select Study and
press Generate
aCRF
Select Undo to revert last
step
Select EDC System
dependent on study location
Select Internal for Test Review and Submission
for Final Submission
Select Production or
QC environment
Tick to receive
email with link to aCRF
aCRF Creator Output
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Process manual vs automated SDTM annotation
17Advancing SDTM annotation through automation | Nov 2020 | Company Confidential © 2020 AbbVie |
Manual Process
AutomatedProcess
aCRF creator – Challenges
18Advancing SDTM annotation through automation | Nov 2020 | Company Confidential © 2020 AbbVie |
Challenges
Interpret XML file
from EDCSystem
Build SAS datasets based on Metadata
Handle characters
outside extended ASCII char
setBuild CRF based on metadata
Create annotations
without overlapping
the CRF labels
Annotate forms
with more than one domain
Study specific
deviations
aCRF creator – Business Impact
19Advancing SDTM annotation through automation | Nov 2020 | Company Confidential © 2020 AbbVie |
Gain in efficiency – annotation done in several minutes
Users can create annotated CRFs ad hoc without waiting time
More user-friendly way to provide higher quality feedback
Bookmarking automation reduces the processing time, prevents transcription errors and inconsistency
Better use of highly qualified personnel
Better quality annotated CRFs
20Advancing SDTM annotation through automation | Nov 2020 | Company Confidential © 2020 AbbVie |
Thank you!
Questions?anja.kreis@abbvie.com